The overall objective of this proposal is to investigate the immunological mechanisms involved in chronic neurological diseases which have a presumed viral etiology. Although its etiology remains unknown, the pathogenesis of multiple sclerosis (MS) is beleived to have both immunological and a virological component. Attempts have been made to demonstrate aberrant immune responses to specific antigens, and particularly to viral antigens, by lymphocytes from MS patients. My preliminary work has shown that in normal measles-immune donors, measles antigens can regulate certain immune functions by the induction of suppressor activity in vitro. The suppression, which is not genetically restricted, appears to be induced by measles and not by other viral antigens. Interferons, released by the lymphocytes in response to treatment with measles antigens are the probably mediators of this suppression. Futher evidence is provided which suggests that null cells, possibly natural killer cells, are the lymphocytes responsible for suppression and interferon production. In marked contrast to normal donors, patients suffering from MS exhibit an almost total absence of measles-induced lymphocyte suppression and interferon production. Thus there appears to be a selective defect in the ability of MS patients to respond appropriately to measles antigens. The aims of this research proposal are to determine: 1) the mechanisms of measles-induced suppression, and in particular the roles of interferons in this system; 2) the nature of the defects in suppression and interferon production in MS patients, including their antigenic and disease specificities; 3) whether MS patients exhibit normal natural killer cell activity in vitro and respond appropriately to interferon inducers and interferon; and 4) the influence of genetic and/or immunoregulatory controls over measles-induced suppression and interferon production.